2-aryl-4-substituted-amino-5-pyrimidyl derivatives

ABSTRACT

AND -(CH2)n-Z, in which R3 and R4 are independently -H, lower alkyl or perfluoro-lower alkyl radicals, with the proviso that when R and R2 are -H, R3 is lower alkyl, Z is -H or -OH, and N IS ONE OF THE INTEGERS 3 OR 4; AND PHARMACEUTICALLY ACCEPTABLE ACID ADDITION SALTS THEREOF.   IN WHICH R,R1 and R2 are independently selected from the group consisting of -H and lower alkyl radicals; X is a member selected from the group consisting of -CH2OH, CHO, -CO2R5, in which R5 is -H or lower alkyl, Y is a member selected from the group consisting of   Compounds of the following formula possess central nervous system depressant properties in warm blooded animals:

United States Patent 11 1 Kim et al.

[ 1 Jan. 14,1975

I 54 l 2-ARYL-4-SUBSTITUTED-AMINO-5- PYRI MIDYL DERIVATIVES [75]Inventors: Dong H. Kim, Wayne; Arthur A.

Santilli, Havertown, both of Pa.

[73] Assignee: American Home Products Corporation, New York, NY.

22 Filed: Aug. 31, 1972 21 Appl. No.: 285,154

[52] US. Cl. 260/256.4 N, 260/244 R, 424/248,

424/251 [51] Int. Cl C07d 51/42 [58] Field of Search 260/256.4 N

[56] References Cited UNITED STATES PATENTS 3,563,984 2/l97l Kim et al.260/244 OTHER PUBLICATIONS Juby et al, J. Med. Chem., 10, 954-956,(1967).

Primary ExaminerRaymond V. Rush Attorney, Agent, or Firm-Richard K.Jackson [57] ABSTRACT Compounds of the following formula possess central7 nervous system depressant properties in warm blooded animals:

X l N i R in which R,R and R are independently selected from the groupconsisting of H and lower alkyl radicals;

X is a member selected from the group consisting of CH OI-I, CI-IO, CO Rin which R is H or lower alkyl,

Y is a member selected from the group consisting of pharmaceuticallyacceptable acid addition salts thereof.

8 Claims, No Drawings 2-ARYL-4-SUBSTITUTED-AMINO -PYRIM IDYL DERIVATIVES BACKGROUND OF THE INVENTION BRIEF DESCRIPTION OF THE INVENTION Inaccordance with this invention, there is provided a group of chemicalcompounds which produce central nervous system depressant effects whenadministered to warm blooded animals, processes for their production,methods for their administration and administrable compositions.

The compounds of this invention may be depicted by the structuralformula:

in which R, R and R are independently selected from the group consistingof -H and lower alkyl radicals; X is a member selected from the groupconsisting of -CH OH, -CHO,

-CO R in which R is -H or lower alkyl, Y is a member selected from thegroup consisting of R and -(CH ),,-Z, in which R and R are independently-H, lower alkyl or perfluoro-lower alkyl radicals, with the proviso thatwhen R and R are -H, R is lower alkyl, Z is -H or -OH, and

n is one of the integers 3 or 4; and pharmaceutically acceptable acidaddition salts thereof.

The expression lower alkyl used throughout the specification, is used toinclude straight and branched chain univalent hydrocarbon radicalscontaining from 1 to 7 carbon atoms, such as methyl, ethyl, ipropyl,n-propyl, n-butyl, n-hexyl, and the like. The expressionpharmaceutically acceptable acid addition salts is used to include thosenon-toxic acid addition salts which may be formed with both organic andinorganic acids such as hydrochloric, hydrobromic, sulfuric, phosphoric,methane sulfonic, nitric, p-toluene sulfonic, acetic, citric, maleic,succinic, and the like..

The compounds of this invention are prepared by reacting an arylamidinehydrochloride with a dialkyl 2- alkoxymethylene alkanedioate NH 1 2 m0CO Et c NH HCl+ c: c\

1 CO Et 1 N (30 m I followed by displacement of the 4-hydroxyl groupwith chlorine by reaction of PCI PCI SOCI POCl and the like, anddechloroamination with either an aromatic amine of the formula 3 /R #E Nan aliphatic amine of the formula H N(CH ),,Z, where the groups R, R ,,RR, R and Z and the value of n are hereinabove defined. Thus, the

amine reactants are desirably aniline, mtrifluoromethylaniline,2,3-dimethylaniline, methylamine, ethylamine, propylaminc, 3-

hydroxypropylamine, butylaminc, N-cthylanilinc, N-

methyl-3-trifluoromethylaniline, N-ethyl-3- trifluoroaniline, and thelike.

An especially useful aliphatic amine is 3- hydroxypropylamine, which maybe cyclized through the ortho carboxyl group in the presence of anacetylating agent such as acetic anhydride to form the lactonel,3-oxazino-[2,3-b]pyrimido[4,5-d][1,3]oxazin-5-one.

The 5-carboalkoxy substituent of the pyrimidine nucleus may be reducedselectively by a reagent such as LiAlI-I, or (t-butoxy) -,LiAlI-I toafford the 5- hydroxymethyl compound, which undergoes mild oxidationwith a reagent such as Mn0 to yield the 5- aldehydo compound.

The compounds of this invention are physiologically active centralnervous system depressants. The compounds were evaluated in accordancewith the following test procedures, the biological activity of thespecifically exemplified compounds being presented in conjunction withthe specific preparative procedure, infra:

PROCEDURE I The compounds were administered orally and intraperitoneallyto-three mice (14 to 24 grams) at doses ranging from 0.04 to 400milligrams per kilogram of host body weight. The animals were watchedfor a minimum of two hours during which time signs of generalstimulation (i.e., increased spontaneous motor activity, hyperactivityon tactile stimulation, twitching), general depression (i.e., decreasedspontaneous motor activity, decreased respiration) and autonomicactivity (i.e., miosis, mydriasis, diarrhea) were noted.

The compounds tested were found to be physiologically active compoundsin experimental and comparative pharmacology and are of value in thetreatment of mammals, e.g., mice, rats, etc., who are responsive totreatment with central nervous system depressant agents. Specificallythe compounds may be administered for the purpose of inducing a calmingeffect in mammals.

The compounds of this invention are individually unique in theiractivity as anti-inflammatory agents. The pertinent testing proceduresby which antiinflammatory activity was evaluated are as follows:

PROCEDURE II From 1.0 to 100 milligrams of the compound tested perkilogram body weight was administered orally to six rats (120-l 60 gramsin weight, averaged between groups) with a six rat control beingadministered aqueous vehicle with no active compound. 60 minutes afterdrug administration, edema was induced by injection of 0.05 millilitersof 1 per cent carrageenin solution into the subplantar tissue of therats right hind paw. The paw volume was immediately volumetricallydetermined with a plethysmograph and again 3 hours later. The meanvolume swelling for the control group was determined and compared to thetest group. Swelling inhibition of 23 per cent or more was considered tobe indicative of an active compound.

PROCEDURE III I This procedure is a modification of the proceduredisclosed in Mizushima, Arch. In. Pharmacodyn., vol. 149, pp. 1-7(1964).

Test solutions are prepared to contain 2.5 milliliters of buffered 1 percent albumin (bovine serum Fraction V) and 2.5 milliliters of buffer orthe solution being tested. The buffer solvent consists of 0.05 molartris(hydroxymethyl)amino methane, (pH6.5). Up to 2.5 per cent finalsolution concentration dimethylformamide may be employed to solubilizethe compound being tested. The control and test systems are heated at69C for 4 minutes, cooled and their turbidities are read at 54millimicrons. Test compounds that decrease the solution turbidity morethan 20 per cent at a concentration up to 1 milligram per liter aredeemed active.

PROCEDURE IV This procedure is a modification of the procedure of Gerberet al., Biochem. Pharmacol, vol. 16, pp. 115-123 (1967).

A mixture of 3 milliliters of 2.07 millimolar solution of the testcompound, 3 milliliters of 4.1 per cent human serum albumin (FractionV), and 0.2 milliliters of 2 millimolar 5,5-dithiobis(2-nitrobenzoicacid) in 0.1 molar aqueous potassium phosphate buffer solution (pH 7.4)is incubated at 30C. The reaction rates are measured for 40 minutes byreading absorbance at 4l2 millimicrons. The net per cent increaseproduced by the test compound is calculated for and 30 minute periods. Aminimum per cent acceleration denotes activity of the test compound at amaximum concentration of 1 milligram per liter. In theory, theantiinflammatory agent accelerates the disulfidesulfhydryl interchangein serum albumen as is evidenced by an increase in the formation ofpigmented 5-thio-2-nitro benzoic acid from serum albumin and5,5-dithiobis(2- nitrobenzoic acid).

PROCEDURE V This test is a modification of the procedure of Skidmore etal., J. Pharm. Pharmacol, vol. 17, pp. 671-673 (1965).

A reaction mixture is prepared to contain 2.0 milliliters of 2.01 percent bovine serum albumin (Fraction V), 2.0 milliliters of 0.15millimolar 2,4,6- trinitrobenzaldehyde, and 2.0 milliliters of a 3.0millimolar (or less) solution of the test compound, all in 0.1 molarsodium phosphate (pH 7.5). Dimethylformamide may be present up to 3 percent of the final volume to facilitate solubilization. The rate ofreaction is measured at room temperature by reading the absorbance at425 and 525 millimicrons over a 40 minute period. The net per centinhibition of color formation is calculated at 30 minutes for both wavelengths and averaged. A compound that decreases the color formation bymore than 20 per cent at l milligram per liter is considered to beactive.

When the compounds of the invention are employed as described above theymay be administered alone or in combination with pharmacologicallyacceptable carriers, the proportion of which is determined by the chosenroute of administration and standard pharmaceutical practice. Forexample, they may be administered orally in tablet or capsule form withconventional flavors, diluents, lubricants, disintegrators or bindingagents as may be required. They may be administered orally in the formof a solution or they may be injected parenterally. For parenteraladministration they may be used in the form of a sterile solutioncontaining other solutes, for example, enough saline or glucose to makethe solution isotonic. It is most advantageous to provide the compoundas a dry powder in a suitable container so that it may be admixed with asuitable aqueous vehicle prior to administration.

Tablets containing the central nervous system depressants of thisinvention may be formulated by admixing a unit dosage amount of theactive compound with microcrystalline cellulose N.F.; magnesium stearateU.S.P.; and a filler such as lactose U.S.P. to obtain any desiredultimate tablet weight. Furthermore, to prepare injectable formulations,the acid addition salt of the desired compound of compound mixture ofthis invention is combined with lactose U.S.P. to form a packageable(sealed glass ampoule, or the like) mix which, when combined with theinjection vehicle, such as sterile water containing about 1 per centbenzyl alcohol and 0.6 per cent sodium acetate/acetic acid buffer, maybe parenterally employed. The specific formulation, for tablets,capsules or injectables depends upon the host and formulation techniquesemployed.

DETAILED DESCRIPTION OF THE INVENTION The following Preparations 1-3illustrate the technique employed to prepare the intermediates fromwhich the biologically active compounds of this invention, presented inExamples 1 11, were prepared.

PREPARATION l Ethyl 4-chloro-6-methyl-2-phenyl-5- pyrimidinecarboxylate.

With vigorous stirring, add 7.8 grams of benzamidine hydrochloride to afreshly prepared solution of sodium ethoxide (2.3 grams sodium inmilliliters absolute ethanol). Add 1 1.5 grams diethylethoxyethylidenemalonate to the mixture and reflux for 1% hour. Chillthe reaction mixture and filter to remove inorganic salts. Evaporate thefiltrate to dryness under reduced pressure. Dissolve the residue inwater and acidify the solution with hydrochloric acid. Collect theprecipitate and recrystallize from ethyl acetate to obtain 3.6 grams ofthe title compound which exhibits an uncorrected melting point of174176C.

Elemental Analysis: C H N O Calculated: C, 65.10; H. 5.46; N. 10.85.Found: C, 65.25; H. 5.45; N. 10.88.

Reflux a mixture of the product of the preceding paragraph (5.7 grams)and phosphorus oxychloride (6O milliliters) for 3.5 hours. Remove theunreacted phosphorus oxychloride under reduced pressure. Treat theresidual oil with crushed ice to obtain 5.2 grams of ethyl4-chloro-6-methyl-2-phenyl-5- pyrimidinecarboxylate as a yellow solid.

PREPARATION II Ethyl 4-chloro-2-phenyl-5-pyrimidinecarboxylate Byfollowing the instruction of Procedure I, with the exception thatdiethyl ethoxymethylenemalonate is used as the reactant in lieu ofdiethyl ethoxyethylidenemalonate, yields 5-carbethoxy-4-hydroxy-2-phenylpyrimidine which may be dehydroxychlorinated to the 4-chloroderivative (Kim & Santilli, J. Heterocycl. Chem, vol. 6. pp. 819-828(1969).

PREPARATION III N-lower alkyl-a,a,a-trifluoro-m-toluidine.

Acetylate a,a,a-trifluoromethyl-m-toluidine (32 grams) by adding theretoin dropwise manner 22 grams of acetic anhydride while stirring themixture. After the exothermic reaction subsides, heat the mixture on asteam bath for 20 minutes. Cool the mixture. Filter the product and washit with water. Recrystallize the product from diethylether-petroleumether to yield 29 grams of N-acetyl-a,a,a-trifluoro-m-toluidine meltingat l01l03C.

Elemental Analysis: C H F NO Calculated: C. 53.20; H, 3.9

7'. N. 6.89 Found: C. 52.96; H, 4.06; N. 6.85

Reduce 30.5 grams of the product of the preceding paragraph with 5.7grams of lithium aluminum hydride in tetrahydrofuran to give 17 grams ofN-ethyl-a,a,a' trifluoro-m-toluidine which has a boiling point of 40C.at 0.75 millimeters mercury pressure.

Elemental Analysis: C H F N Calculated: C. 57.74; H, 5.38; N. 7.48Found: C. 57.09; H. 5.26; N. 7.51

Following the above detailed procedure, various N- loweralkyl-a.a,a-trifluoro-m-toluidine derivatives such as the N-propyl andN-butyl compounds may be prepared.

The following examples present specific instructions in accordance withwhich the compound aspects ofthis invention were prepared.

EXAMPLE I Ethyl 4-methyl-2-phenyl6-(a,a,a-trifluoro-mtoluidino)-5-pyrimidinecarboxylate.

Reflux a mixture of ethyl 4-chloro-6-methyl-2phenyl-S-pyrimidinecarboxylate (2.6 grams), a.a,a-trifluoro-m-toluidine(10 milliliters) and ethanol 15 milliliters) for 2 hours. Cool thereaction mixture, filter the precipitate and wash the product withwater. Crystallize the product from ethanol to obtain 2.5 grams of thetitle compound which has a melting point of -123C.

Elemental Analysis: C H F N O Calculated: C. 62.84; H. 4.52; N. 10.47Found: C. 62.93; H. 4.53. N. 10.52

EXAMPLE II Elemental Analysis: C H F N O Calculated: C. 61.13. H. 3. .N.

8 11.29 Found: C. 61.00; H. 3.88; 11.41

This carboxylic acid is a central nervous system depressant,demonstrating activity at a dosage level of 127 milligrams per kilogrambody weight and above. The activity noted in mice, upon oraladministration in accordance with Test Procedure No. 1, supra, decreasedmotor activity, sedation, decreased respiration and hyperemia. Inaddition, anti-inflammatory activity was observed in vivo and in vitroin accordance with the Test Procedures No. II, III at 0.09 millimolarconcentration and V at 0.3 millimolar concentration supra.

EXAMPLE III 2-Phenyl-4-(2,3-xylidino)-5-pyrimidinecarboxylic acid andthe ethyl ester thereof Following the technique of Example I react 2,3-xylidine and ethyl 4-chloro-2-pheny1-5- pyrimidinecarboxylate to yieldthe ethyl ester which is hydrolyzed to afford the free acid.

EXAMPLE 1V Ethyl 4-(N-ethyl-a,a,a-Trifluoro-m-to1uidino)-2-phenyl-S-pyrimidinecarboxylate Reflux a mixture of5-carbethoxy-4-chloro-2- phenylpyrimidine (6.5 grams),N-ethyl-a.a,a-trifluorom-toluidine (5 grams), sodium carbonate (2.7grams) and N.N-dimethyl formamide (45 milliliters) for 3.5 hours. Pourthe reaction mixture into cold water to separate the product as an oil.Wash the oil several times with water and cool to cause solidification.Filter and wash with diethyl ether to obtain 4.0 grams of product whichupon recrystallization from petroleum ether affords the title compoundmelting at 100102C.

Elemental Analysis: c n F n o Calculated: C, 63.61; H. 4.85; N, 10.12Found: C, 63.27; H, 514; N, 10.22

The ester prepared in accordance with the preceding Example exhibitedanti-inflammatory activity at a minimum concentration of 0.8 millimolesper liter in accordance with Test Procedure No. 111.

EXAMPLE V 4-(ethyl-0 1,a-trifluoro-metoluidine)-2-phenyl-5-pyrimidinecarboxylic acid Heat a mixture of the ethyl ester of ExampleIV (1.5

grams), 50 per cent aqueous dimethylsulfoxide (75 milliliters), 15 percent aqueous sodium hydroxide solution (4.5 milliliters) and millilitersof dimethylsulfoxide on a steam bath for 6 hours. Allow the temperatureof the mixture to fall to room temperature and acidify with 3N HCl toprecipitate the free acid. Filter and wash with water to yield 1.4 gramsof the title compound. An analytically pure compound melting at 180-l82C. is obtained by recrystallization from aqueous ethanol.

Elemental Analysis: C H F N O Calculated: C, 62.01; H, 4.16; N, 10.80Found: C, 61.59; H, 4.07; N, 10.85

The free acid prepared by the method presented in the precedingparagraph produced a central nervous system depressant effect whenadministered orally and intraperitoneally at doses as low as 127milligrams per kilogram host body weight, to mice, as evidenced bydecreased motor activity, decreased respiration mydriasis and hyperemia.Furthermore, the free acid produced an anti-inflammatory effect whentested in accordance with Procedures III at 0.03 millimolar minimaleffect and V at 0.08 millimolar concentration.

EXAMPLE VI Elemental Analysis: C H N O Calculated: C, 63.77; H, 6.36; N,13.95 Found: C, 63.65; H, 6.49; N, 13.99

The product of the preceding example produces central nervous systemdepressant effects on mice when administered orally at a concentrationas low as 127 milligrams per kilogram host body weight as evidenced byhyperactivity to touch decreased motor activity, sedation and decreasedrespiration.

EXAMPLE Vll 4-(3-Hydroxypropylamino)-2-phenyl-5'- pyrimidinecarboxylicacid Reflux a mixture of the ethyl ester of Example VI (15 grams), 15per cent aqueous NaOH solution (45 milliliters), and ethanol (10milliliters) for 0.5 hour. Adjust the pH of the solution to about 2 byadding HCl, thereby precipitating the free acid. Filter and wash withwater to obtain 8.0 grams of product having a melting point of 223225C.Further purification of the title compound by dissolving in basefollowed by acidification yields a product melting at 228230C.

Elemental Analysis: C, H, N -,O

Calculated: C. 61.53; H, 5.53; N. 15.38 Found: C, 61.33; H, 5.66; N.15.61

4-(3-Hydroxypropylamino)-2-phenyl-5- pyrimidinecarboxylic acid producedcentral nervous system depressant effects in mice when oral doses as lowas 127 milligrams per kilogram body weight are administered. Theobserved effects are decreased motor activity, sedation, decreasedrespiration, augmented flexor, reflex, mydriasis and hyperemia. Inaddition, the free acid produces an anti-inflammatory effect upon oraladministration to rats in accordance with Test Procedure II.

EXAMPLE VIII 9,10-Dihydro-6a-methyl-2-phenyl-5H,6aH,8H-[1,3]oxazino[-2,3b]-pyrimido[4,5-d][1,3]oxazin-5-one Reflux a mixture of4-(3-hydroxypropylamino)-2- phenyl-5-pyrimidinecarboxylic acid (3 grams)with acetic anhydride (40 milliliters) for about 30 minutes to obtain aclear solution. Remove the acetic anhydride in vacuo to leave a resinousmaterial which crystallized from ethyl acetate after several washingswith anhydrous diethyl ether to afford the title compound melting atl53155C.

Elemental Analysis: C H N o Calculated: C, 64.63; H, 509; N, 14.14Found: C, 64.66; H, 5.06; N, 13.95

The lactone l,3-oxazino[2,3-b]pyrimido[4,5- d][1,3]-oxazin-5-oneproduces central nervous system depressant activity when administeredintraperitoneally to mice in doses as low as 40 milligrams per kilogrambody weight, as evidenced by decreased motor activity and decreasedrespiration.

EXAMPLE 1X 2-Phenyl-4-(a,a,a-trifluoro-m-toluidino)-5-pyrimidinemethanol.

Reduce 15.3 grams of ethyl2-phenyl-4-(a,a,atrifluoro-m-toluidino)-5-pyrimidinecarboxylate with 1.6grams of LiAlH; using tetrahydrofuran as the reaction solvent. Afterhours reaction time, the crude product weighed 13.8 grams.Crystallization from ethanol yielded an analytically pure sample meltingat 174-177C.

Elemental Analysis: C,,,H,,F,N,0

Calculated: C. 62.61; H. 4.09; N, 12.17 Found: C, 62.61; H, 4.12; N,12.10

The product of the preceding example produces central nervous systemdepressant effects in mice when administered intraperitoneally in dosesas low as 40 milligrams per kilogram host body weight, evidenced bydecreased motor activity, decreased respiration and ataxia at a dose aslow as 400 milligrams per kilogram body weight.

EXAMPLE X 2-Phenyl-4-(2,3-xylidino)-5-pyrimidinemethanol Following theprocedure of Example lX, reduce 13.5 grams of ethyl2-phenyl-4-(2,3-xylidino)-5- pyrimidinecarboxylate with 2.0 grams ofLiAll-L, in 250 milliliters of tetrahydrofuran to obtain 1 1 grams ofthe title compound which melts at l70l 74C. Recrystallization fromethanol yields the compound melting at l72l74.5C.

Elemental Analysis: C H N O Calculated: C. 74.73; H. Found: C. 74.49; H.

The product of Example X produces central nervous system depressanteffects in mice when administered orally in doses as low as 400milligrams per kilogram and intraperitoneally in doses as low as 127milligrams per kilogram host body weight. Thus, the depressant effectsare observed in hyperactivity to touch, decreased motor activity,ataxia, decreased respiration and ptosis.

EXAMPLE XI Elemental Analysis: C H F N O Calculated: C. 62.67; H. 3.53;N. I224 Found: C. 62.63; H. 3.42; N, ll.97

The product of Example X produces central nervous system depressanteffects in mice at oral doses as low as 12.7 milligrams per kilogramhost body weight, evidenced by decreased motor activity sedation anddecreased respiration.

What is claimed is:

1. A compound of the formula:

in which R is -H or lower alkyl.

2. The compound of claim -1 which is 4-methyl-2-phenyl-6-(a,a,a-trifluoro-m-toluidino)-5- pyrimidinecarboxylic acid.

3. A compound of the formula 5 N CO2R CF C2H5 s in which R is -H orlower alkyl.

4. The compound of claim 3 which is4-(N-ethyla,a,ot-trifluoro-m-toluidino)-2-phenyl-5- pyrimidinecarboxylicacid.

5. A compound of the formula:

N ECX in which X is -CH OH or -CHO; R is -H or alkyl of l to 7 carbonatoms; and R is -H, alkyl of l to 7 carbon atoms or perfluoroalkyl of 1to 7 carbon atoms.

6. The compound of claim 5 which is 2-phenyl-4-(a,a,a-trifluoro-m-toluidino)-5-pyrimidinemethanol.

7. the compound of claim 5 which is 2-phenyl-4-(2,3-

xylidino)-5-pyrimidinemethanol.

8. The compound of claim 5 which is 2-phenyl-4-(a,a,a-trifluoro-m-toluidino)-5- pyrimidinecarboxaldehyde.

2. The compound of claim 1 which is 4-methyl-2-phenyl-6-( Alpha , Alpha, Alpha -trifluoro-m-toluidino)-5-pyrimidinecarboxylic acid.
 3. Acompound of the formula
 4. The compound of claim 3 which is 4-(N-ethyl-Alpha , Alpha , Alpha-trifluoro-m-toluidino)-2-phenyl-5-pyrimidinecarboxylic acid.
 5. Acompound of the formula:
 6. The compound of claim 5 which is2-phenyl-4-( Alpha , Alpha , Alpha-trifluoro-m-toluidino)-5-pyrimidinemethanol.
 7. the compound of claim 5which is 2-phenyl-4-(2,3-xylidino)-5-pyrimidinemethanol.
 8. The compoundof claim 5 which is 2-phenyl-4-( Alpha , Alpha , Alpha-trifluoro-m-toluidino)-5-pyrimidinecarboxaldehyde.